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Background and Objectives: The purpose of this study is to assess the long-term maintenance of each approach of sinus elevation, the crestal approach and lateral approach, by comparing the radiographic results of each technique. Materials and Methods: In total, 103 patients who had undergone an implant procedure with either the crestal approach or lateral approach method applied to their maxillary molar edentulous area were included. Using orthopantomographs, the radiographic changes were consistently evaluated over 3 years after the procedure (immediately after procedure and 1 year, 2 years and 3 years after implant placement) Results: The radiographic evaluation after 3 years of implantation with sinus elevation showed a significant amount of bone formation (8.07 mm for crestal approach and 12.00 mm for lateral approach method). The largest amount of grafted height loss occurred during the 1 year, but the resorption was minimal (0.98 mm for crestal approach and 0.95 mm for lateral approach method) over the entire 3 years. Conclusions: Although the lateral approach showed more bone growth, the amount of bone resorption was similar to that of the crestal approach. Both methods showed the highest amount of bone resorption in the first year, and the amount of change thereafter was insignificant. It is judged that both methods can be used according to the situation to help implant placement.

The hydrophilicity of bone graft material generally used as a carrier can play an important role in regulating bone morphogenetic protein (BMP) expression at the bone graft site. The hydrophilicity, altering physicochemical properties, and enhancing biological capabilities, can be increased via surface modification through ultraviolet (UV) photofunctionalization and the effect on de novo osteogenesis could be further improved. Therefore, this study aimed to assess the effects of UV-irradiated TiO2 -coated hydroxyapatite (HA) in combination with rhBMP-2 on bone regeneration in rabbit calvarial defects. The hydrophilicity of HA and TiO2 -coated HA pellets was evaluated by measuring the contact angle of water droplets with UV irradiation. To compare de novo osteogenesis in rabbit calvarial defects, the rabbits were segregated into four different groups: negative control, HA, TiO2 -coated HA, and TiO2 -coated HA with UV; histomorphometric analysis and micro-computed tomography (μCT) imaging were performed after 4 and 8 weeks. In vivo analysis revealed that de novo osteogenesis occurred on the critical size defects in all groups and was significantly increased in the TiO2 -coated HA with UV group than in other groups (p < 0.05). The present results indicate that UV photofunctionalization promotes de novo osteogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1953-1959, 2019.

Objective To evaluate the effect of resveratrol on periodontal bone regeneration after local delivery and to determine its effect on inflammatory mediators. Background Resveratrol is considered an anti-inflammatory polyphenolic stilbene involved in the modulation of inflammation. Materials and methods Periodontitis was induced in mouse molars using a 5-day ligature model followed by the left second molar extraction and 50 µM resveratrol treatment for 1 and 2 weeks. We then examined specimens treated for 1 week histologically and with immunostaining. Microfocus-computed tomography (micro-CT) was used to examine the bone volume formation. Results After 1 week of treatment, proinflammatory cytokine levels (TNF-alpha and IL6), cells exhibiting neutrophil and macrophage marker (MPO), cell proliferation marker (Ki67), and preosteoblastic marker (RUNX2) reactivity decreased in the resveratrol-treated specimens compared to the control group. In contrast, we observed a higher number of CD31-, F4/80-, and osteocalcin- (OCN-) positive cells in the resveratrol-treated specimens. After 2 weeks, micro-CT confirmed an increased bone mass in the region of the extraction socket in the resveratrol-treated group. Conclusion After 1 week, the resveratrol-treated specimens revealed evidence of inflammation modulation compared to the control group. These data suggest that resveratrol not only affects inflammation control but also is useful for treating periodontitis-related tissue defects and bone regeneration.

The endoplasmic reticulum (ER) is a site where protein folding and posttranslational modifications occur, but when unfolded or misfolded proteins accumulate in the ER lumen, an unfolded protein response (UPR) occurs. A UPR activates ER-stress signalling genes, including inositol-requiring enzyme-1 (Ire1), activating transcription factor 6 (Atf6), and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (Perk), to maintain homeostasis. The involvement of ER stress molecules in metabolic disease and hard tissue matrix formation has been established; however, an understanding of the role of ER-stress signalling molecules in tooth development is lacking. The aims of this study are to define the stage-specific expression patterns of ER stress-related molecules and to elucidate their putative functions in the organogenesis of teeth. This study leverages knowledge of the tissue morphology and expression patterns of a range of signalling molecules during tooth development. RT-qPCR, in situ hybridization, and immunohistochemistry analyses were performed to determine the stage-specific expression patterns of ER-stress-related signalling molecules at important stages of tooth development. RT-qPCR analyses showed that Atf6 and Perk have similar expression levels during all stages of tooth development; however, the expression levels of Ire1 and its downstream target X-box binding protein (Xbp1) increased significantly from the cap to the secretory stage of tooth development. In situ hybridization results revealed that Atf6 and Xbp1 were expressed in cells that form the enamel knot at cap stage and ameloblasts and odontoblasts at secretory stage in stage-specific patterns. In addition, Atf6, Ire1, and Xbp1 expression exhibited distinct localization patterns in secretory odontoblasts and ameloblasts of PN0 molars. Overall, our results strongly suggest that ER-stress molecules are involved in tooth development in response to protein overload that occurs during signaling modulations from enamel knots at cap stage and extracellular matrix secretion at secretory stage.

Purpose To investigate factors affecting the antagonistic and adjacent teeth in patients after implant restoration and prosthetic rehabilitation. Methods In total, 160 patients who visited Kyungpook National University Dental Hospital for implant surgery, prosthesis placement, and supportive periodontal therapy (SPT) were included in this study. The average follow-up period was 88.06 months, and the maximum was 175 months. Patients’ history of smoking, diabetes, hypertension, and osteoporosis was investigated, and panoramic radiographs were taken after surgery and prosthetic treatment. During the follow-up period, extraction and prosthetic/endodontic treatments of the antagonistic and adjacent teeth were analyzed. The statistical analyses were performed using descriptive statistics, the chi-square test, the Fisher exact test, and multiple logistic regression analyses. Results Treatment was performed on 29.4% of the studied antagonistic teeth with extraction performed in 20.0% and prosthetic treatment in 10.0%. Furthermore, 19.4% of the studied adjacent teeth underwent treatment, of which extraction was performed in 12.5% and prosthetic treatment in 7.5%. The treatment rate for adjacent teeth was 25.3% in smokers, which was higher than that of non-smokers (12.3%) (P=0.039). Patients who were non-adherent to SPT showed a significantly higher rate (19.6%) of antagonistic prosthetic treatment than did those who were adherent (5.5%) (P=0.006). Conclusions Implant restoration can affect the adjacent and antagonistic teeth. Smoking, osteoporosis history, and absence of SPT may be risk factors for the treatment of the adjacent and antagonistic teeth., Graphical Abstract

Although increasing evidence indicates that serotonin (SER; 5-hydroxytrypamine [5-HT]) is involved in the regulation of bone metabolism, conflicting data exist regarding whether SER promotes or inhibits osteoblast differentiation and bone formation. Regeneration of functional bone is required for proper osseointegration of dental implants. Noticeably, the use of selective SER reuptake inhibitors was recently associated with the failure of osseointegrated dental implants. The present study examines the direct role of peripheral SER on the regulation of bone regeneration.The effect of SER on osteoblast differentiation and bone regeneration was examined using rat calvarial cell cultures in vitro and a rat critical-sized calvarial defect model in vivo.Rat calvarial cells expressed SER receptors Htr1 (5-HT1) and Htr2 (5-HT2), which are known to transmit signals in bone cells. In vitro, SER significantly reduced osteogenic differentiation and mineralization of rat calvarial cells with concomitant reduction of osteoblast marker genes including alkaline phosphatase (Alpl), osterix (Sp7), and osteocalcin (Bglap). Histologic and radiologic analyses using the rat critical-sized calvarial defect model revealed that the existence of SER significantly inhibited β-phase tricalcium phosphate-induced bone regeneration.Results suggest that SER in the local bone microenvironment might play a negative role in osteoblast differentiation and bone formation in rats.

Purpose This randomized controlled study aimed to evaluate the effects of an electric toothbrush with 3 colors of light-emitting diodes (LEDs) on antiplaque and bleeding control. Methods This randomized, placebo-controlled, double-blinded, parallel-group clinical trial included 50 healthy adults with gingivitis, who were randomly assigned to 2 groups. The experimental group used electric toothbrushes with 3 colors of LEDs and the control group used the same electric toothbrush as the experimental group, but with LED sources with one-hundredth of the strength. The subjects used the electric toothbrush 3 times a day for 4 minutes each time. As clinical indices, bleeding on marginal probing (BOMP), the Löe-Silness gingival index (GI), and the Turesky-Quigley-Hein plaque index (QHI) were assessed at baseline, at 3 weeks, and at 6 weeks. Results There were significant decreases in all clinical indices (BOMP, GI, QHI) in both the experimental and control groups compared to baseline at 3 weeks and at 6 weeks. In a comparison between the experimental and control groups, no statistically significant differences were observed for any clinical indices at 3 weeks (P>0.05). However, at 6 weeks, statistically significant differences were observed between the experimental and control groups in BOMP and GI, which are indicators of gingival inflammation (P, Graphical Abstract

Purpose Hydroxyapatite treated with recombinant human bone morphogenetic protein-2/Hydroxyapatite (rhBMP-2/HA) or bovine bone was applied on extraction sockets for alveolar ridge preservation, and the results were compared with respect to clinical and histological bone formation. Materials and methods This was a prospective, randomized controlled clinical trial performed on 20 implant placement sites (10 in the experimental and 10 in the control group). rhBMP-2/HA was applied on extraction sockets in the experimental group and bovine bone on those of the control group. The bone at the corresponding sites was biopsied 3 months later, and clinical, histological, and histomorphometric analyses were performed. Results The alveolar bone height was well preserved in both groups with relatively less change in width in the experimental group compared with the control group. The percentage of new bone was 25.37% ± 17.23% in the experimental group and 6.13% ± 4.32% in the control group; the difference was statistically significant. Conclusions The alveolar ridge was preserved clinically and histologically in both groups. rhBMP-2/HA resulted in greater new bone formation than bovine bone 3 months after the surgery.

Background and objective After tooth extraction, the extraction socket undergoes several steps of soft and hard tissue healing. The healing process of the extraction socket is modulated by a range of signaling factors and biochemical agents. It has been reported that resveratrol, a polyphenolic compound, exhibits various biological effects, including anti-inflammatory, anti-carcinogenic, antioxidant, and anti-aging effects, and protects cardiovascular and bone tissues. In this study, we examined the cellular effects of resveratrol on human periodontal ligament (hPDL) cells and osteoblast-like (MC3T3-E1) cells and evaluated the bone-healing capacity of tooth extraction sockets in mice. Material and methods Resveratrol was applied to hPDL and MC3T3-E1 cells to detect cell proliferation and alkaline phosphatase (ALP) activity, and qPCR was employed to understand the gene expression level in vitro. For in vivo experiment, six-week-old C57BL/6 male mice were randomly divided into control (n = 15) and experimental (n = 15) groups and maxillary first molars were extracted by surgery. Experimental groups received 50-µM resveratrol on extraction sockets and analyzed the degree of new bone formation. Results Treatment of hPDL and MC3T3-E1 cells with resveratrol increased the cell proliferation and ALP activity and enhanced the expression of ALP, BMP-2, BMP-4, and OC genes. Resveratrol enhanced new bone formation in the lingual extraction socket in mice. Conclusion These results suggest that resveratrol increases the cellular physiology of PDL and osteoblast including their proliferation and differentiation and may play an important role in bone-healing capacity after tooth extraction.

Objective We evaluated the role of oleanolic acid acetate (OAA), a triterpenoid commonly used in the treatment of liver disorders, inflammatory diseases, and metastasis, in bone formation after tooth loss by periodontitis. Background Periodontitis causes the sequential degradation of the alveolar bone and associated structures, resulting in tooth loss. Several studies have attempted to regenerate the bone for implantation following tooth loss. Methods Maxillary left second molar was extracted from 8-week-old male mice following induction of periodontitis by ligature for 5 days. The extraction socket was treated with 50 ng/µL OAA for 1, 2, and 3 weeks. Detailed morphological changes were examined using Masson's trichrome staining, and the precise localization patterns of various signaling molecules, including CD31, F4/80, interleukin (IL)-6, and osteocalcin, were observed. The volume of bone formation was examined by Micro-CT. Osteoclasts were enumerated using tartrate-resistant acid phosphatase (TRAP) staining. For molecular dissection of signaling molecules, we employed the hanging-drop in vitro cultivation method at E14 for 1 day and examined the expression pattern of transforming growth factor (TGF)-β superfamily and Wnt signaling genes. Results Histomorphometrical examinations showed facilitated bone formation in the extraction socket following OAA treatment. In addition, OAA-treated specimens showed the altered localization patterns of inflammatory and bone formation-related signaling molecules including CD31, F4/80, IL-6, and osteocalcin. Also, embryonic tooth germ mesenchymal tissue cultivation with OAA treatment showed the significant altered expression patterns of signaling molecules such as transforming growth factor (TGF)-β superfamily and Wnt signaling. Conclusions Oleanolic acid acetate induces bone formation and remodeling through proper modulation of osteoblast, osteoclast, and inflammation with regulations of TGF-β and Wnt signaling.

The hydrophilicity of bone graft material generally used as a carrier can play an important role in regulating bone morphogenetic protein (BMP) expression at the bone graft site. The hydrophilicity, altering physicochemical properties, and enhancing biological capabilities, can be increased via surface modification through ultraviolet (UV) photofunctionalization and the effect on de novo osteogenesis could be further improved. Therefore, this study aimed to assess the effects of UV-irradiated TiO

Adenomatosis polyposis coli downregulated 1 (APCDD1), a negative regulator of Wnt signaling, was examined to understand detailed mechanisms underlying Wnt signaling tooth development. In situ hybridization showed that Apcdd1 was expressed in the condensed mesenchyme at the bud stage, and in the inner enamel epithelium (IEE), including enamel knot (EK) at the cap stage. In vitro organ cultivation by using Apcdd1 antisense oligodeoxynucleotides was performed at E13.5 for 2 days to define the developmental functions of APCDD1 during tooth development. Analysis of histogenesis and cellular events such as cell adhesion, proliferation, apoptosis and epithelial rearrangement after Apcdd1 knockdown showed altered morphogenesis of the tooth germ with decreased cell proliferation and altered localization of cell adhesion molecules. Actin filament staining and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) labeling of IEE cells showed that Apcdd1 knockdown enhanced epithelial rearrangement in the IEE and EK. To understand the precise signaling regulations of Apcdd1, we evaluated the altered expression patterns of signaling molecules, related with Wnt and enamel knot signalings using RT-qPCR. Tooth germs at cap stage were transplanted into the kidney capsules and were allowed to develop into calcified teeth for 3 weeks. Apcdd1 knockdown increased the number of ectopic cusps on the mesial side of the tooth. Our results suggested that APCDD1 modulates the gene expression of Wnt- and EK-related signaling molecules at the cap stage of tooth development, and is involved in tooth cusp patterning by modulating the epithelial rearrangement in the IEE.

This study was performed to investigate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) during mineralization of human periodontal ligament (hPDL) cells in high glucose conditions. The hPDL cells were cultured in 1000 mg/L d-glucose (normal glucose group) or 4500 mg/L d-glucose (high glucose group) and exposed to rhBMP-2 at concentrations of 0, 50, 100, 300, and 500 ng/mL. MTT assays were performed on days 4 and 7. Alkaline phosphatase (ALP) activity was measured on day 10. On day 28, cells that were stained with alizarin red S and calcium deposition were measured. On days 4 and 7, rhBMP-2 inhibited mitochondrial activity dose-dependently in both groups. On day 10, ALP activity was increased by rhBMP-2 dose-dependently in both groups and had a tendency to inhibit ALP activity in high glucose groups. On day 28, mineralized nodule formation and calcium deposition were increased by rhBMP-2 dose-dependently in both groups and were inhibited at the lower concentration of rhBMP-2 (under 100 ng/mL) but markedly increased at a higher concentration of rhBMP-2 (300 and 500 ng/mL) in high glucose groups. We concluded that it was important to establish the appropriate concentration of rhBMP-2 for the treatment of periodontal disease in diabetic patients.

The alveolar bone process is the thickened ridge of bone that bears the teeth and is known to have dynamic functional interactions with surrounding tissues. However, the detailed morphological changes that occur during alveolar bone process development and the underlying molecular mechanisms behind this morphogenesis have not been elucidated. In this study, we examined the detailed morphological changes of the alveolar bone process during mouse development using HE and MTC staining. In addition, we evaluated the precise localization pattern of various signaling molecules involved in blood vessel formation including CD31, α-SMA, VEGF, periostin, and TGF-β. Innervation of the alveolar bone process was examined following injection of the nerve terminal dye AM1-43. The morphological and immunohistochemical data suggested that there is an intimate relationship between alveolar bone process development and blood vessel formation. To more closely examine the role of blood vessels in alveolar bone process formation, we microinjected mice with a clinically available anti-VEGF antibody, bevacizumab, at PN5 and analyzed the effects 5 days later. Compared to the control animals, anti-VEGF treated animals showed a disruption of the integration of bony tissues to form the alveolar bone process structures, which should contain the periodontal ligaments. Based on these data, we conclude that specific morphogenesis of the alveolar bone process is closely associated with blood vessel formation.

Objective The interleukin-17 (IL-17) family is a group of pro-inflammatory cytokines that are produced by a subset of helper T cells. IL-17 family members are not only involved in the immune response of tissues but also play a role in bone metabolism. Although the role of IL-17 in osteoclast-mediated bone resorption has been extensively studied, its role during osteoblast-mediated bone formation has rarely been investigated. In this study, we examined the effect of IL-17 on osteogenesis in rats both in vitro and in vivo . Design To evaluate osteogenesis in vitro , rat calvarial osteoblast precursor cells were cultured for 14 days in osteogenic medium with or without 50ng/mL IL-17. Osteogenic activity was evaluated by alkaline phosphatase and alizarin red staining. The mRNA expression of alkaline phosphatase, osteocalcin, and osterix was also measured by using real-time PCR. To test whether IL-17 affects bone formation in vivo , bone filling was examined by micro-computed tomography and histological observations at 8 weeks after critical-sized defects were made in rat calvaria. Results The presence of IL-17 significantly reduced alkaline phosphatase and alizarin red staining and the expression of alkaline phosphatase, osteocalcin, and osterix in vitro . IL-17 also significantly inhibited the filling of calvarial defects in vivo . Conclusion IL-17 exerted a negative effect on osteogenesis in a rat model. In contrast to the previously reported beneficial effect on osteogenic differentiation of human mesenchymal stem cells, our results suggest a species or cell type-specific role for IL-17 in bone formation.

Statement of the Problem There is a reported gap between the relative satisfaction of the clinician and patient after a root coverage procedure. In addition, there may also be a disparity between objective esthetic evaluation tools and subjective satisfaction. Methods This study included 58 sites in 31 patients who had undergone root coverage procedures. The percentage of root coverage and the root coverage esthetic score system were used as objective measurements. A questionnaire with a five-point ordinal scale was used for subjective evaluation. Initial recession depth and width, Miller classification, tissue biotype, treatment procedures, and follow-up periods were considered as associated factors. Results After a period of at least 6 months from the procedure, the patient-perceived outcome showed a better match with the root coverage esthetic scoring system than the percentage of root coverage alone. A lower value for objective outcome was obtained for a deeper gingival recession and higher Miller class, but the subjective outcome displayed a steady trend. All four esthetic results were at their lowest after an epithelialized free soft tissue graft. Conclusion An esthetic outcome according to patient satisfaction was not always consistent with that determined by professional scoring. In addition, partial root coverage may be viewed as a positive outcome by patients and clinicians in cases of deep gingival recession and high Miller class. Clinical Significance This study evaluates the esthetic outcome of root coverage procedures using an objective method, including the percentage of root coverage, root coverage esthetic scoring system, and subjective assessment by patient and clinician-based questionnaires. The results will be helpful for the understanding of the differences that exist in esthetic satisfaction.

Aim This study investigated the efficacy of the hypothalamic nonapeptide oxytocin (OT) by direct delivery to local defects using a microporous β-tricalcium phosphate (TCP) as the carrier for the future applications as a method to achieve predictable bone regeneration of large osseous defects requiring sinus bone graft and guided bone regeneration procedures for implant placement. Material and Methods Both the ectopic and new bone formation induced by the OT-loaded microporous β-TCP powder was histomorphometrically compared with unloaded β-TCP in a subcutaneous ectopic bone formation model and calvarial critical-sized defects (CSDs) in 45 rats. Results The OT-loaded β-TCP clearly enhanced ectopic bone formation compared with the unloaded control group. A High initial OT dose (250 μg) significantly increased ectopic bone formation at an early healing time-point compared with a lower OT dose (50 μg). The OT-loaded samples displayed greater new bone formation in the rat calvarial CSDs. Extensive new bone formation was achieved in the calvarial CSDs with the higher OT dose. Conclusion These results suggest that local OT delivery to bone substitute promotes new bone formation via an osteoinductive mode of action.

Purpose: The aim of this study was to evaluate the influence of the crown-to-implant (C/I) ratio on the change in marginal bone level around the implant and to determine the site-related factors influencing the relationship between the C/I ratio and periimplant marginal bone loss. Methods: A total of 259 implants from 175 patients were evaluated at a mean follow-up of five years. Implants were divided into two groups according to their C/I ratios: ≤ 1, and > 1. Site-related factors having an influence on the relationship between C/I ratio and periimplant marginal bone loss were analyzed according to the implant location, implant diameter, implant manufacturer, prosthesis type, and guided bone regeneration (GBR) procedure. Results: It was found that 1) implants with a C/I ratio below 1 exhibited greater periimplant marginal bone loss than implants with a C/I ratio more than 1, 2) site-related factors had an effect on periimplant marginal bone loss, except for the implant system used, 3) the C/I ratio was the factor having more dominant influence on periimplant marginal bone loss, compared with implant diameter, prosthesis type, implant location, and GBR procedure, 4) implants with a C/I ratio below 1 showed greater periimplant marginal bone loss than implants with a C/I ratio greater than 1 in the maxilla, but not in the mandible, 5) and periimplant marginal bone loss was more affected by the implant system than the C/I ratio. Conclusions: Within the limitations of this study, implants with a higher C/I ratio exhibited less marginal bone loss than implants with a lower C/I ratio in the posterior regions. The C/I ratio was a more dominant factor affecting periimplant marginal bone loss in the maxilla than the mandible. Meanwhile, the implant system was a more dominant factor influencing periimplant marginal bone loss than the C/I ratio.

Background Periodontitis is the most common chronic inflammatory disease caused by complex interaction between the microbial biofilm and host immune responses. In the present study, high-throughput RNA sequencing was utilized to systemically and precisely identify gene expression profiles and alternative splicing. Methods The pooled RNAs of 10 gingival tissues from both healthy and periodontitis patients were analyzed by deep sequencing followed by computational annotation and quantification of mRNA structures. Results The differential expression analysis designated 400 up-regulated genes in periodontitis tissues especially in the pathways of defense/immunity protein, receptor, protease, and signaling molecules. The top 10 most up-regulated genes were CSF3, MAFA, CR2, GLDC, SAA1, LBP, MME, MMP3, MME-AS1, and SAA4. The 62 down-regulated genes in periodontitis were mainly cytoskeletal and structural proteins. The top 10 most down-regulated genes were SERPINA12, MT4, H19, KRT2, DSC1, PSORS1C2, KRT27, LCE3C, AQ5, and LCE6A. The differential alternative splicing analysis revealed unique transcription variants in periodontitis tissues. The EDB exon was predominantly included in FN1, while exon 2 was mostly skipped in BCL2A1. Conclusions These findings using RNA sequencing provide novel insights into the pathogenesis mechanism of periodontitis in terms of gene expression and alternative splicing. Electronic supplementary material The online version of this article (doi:10.1186/s40246-016-0084-0) contains supplementary material, which is available to authorized users.

Comparison of up-regulated genes in periodontitis with those of the previous study by Davanian et al. The Venn diagram shows the number of genes unique for each study and that of commonly detected genes. (PDF 388Â kb)

The alternative splicing events in individual samples. The individual variation in alternative splicing events in FN1 and BCL2A1 was examined by RT-PCR analysis of individual healthy and periodontitis samples. (PDF 419Â kb)

The characteristics of patients involved in the current study. The information on age, gender, and disease severity is given in this table. (DOCX 54Â kb)

The expression levels of selected genes in individual samples. The individual variation in gene expression was examined by real-time RT-PCR analysis of individual healthy and periodontitis samples. The p values of the Wilcoxon rank-sum test between healthy and periodontitis groups are given in each graph. (PDF 566Â kb)

Primer sequences used for the RT-PCR validation of RNA sequencing alternative splicing results. The primer sequences are given in this table. (DOCX 50Â kb)

Primer sequences used for the real-time RT-PCR validation of RNA sequencing differential gene expression results. The primer sequences are given in this table. (DOCX 89Â kb)

Different from humans, who have a continuous dentition of teeth, mice have only three molars and one incisor separated by a toothless region called the diastema in the hemi mandibular arch. Although tooth buds form in the embryonic diastema, they regress and do not develop into teeth. In this study, we evaluated the proteins that modulate the diastema formation through comparative analysis with molar-forming tissue by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) proteome analysis. From the comparative and semi-quantitative proteome analysis, we identified 147 up- and 173 down-regulated proteins in the diastema compared to the molar forming proteins. Based on this proteome analysis, we selected and evaluated two candidate proteins, EMERIN and RAB7A, as diastema tissue specific markers. This study provides the first list of proteins that were detected in the mouse embryonic diastema region, which will be useful to understand the mechanisms of tooth development [BMB Reports 2012; 45(6): 337-341]

Objective It is unclear whether surface bioactive chemistry or hydrophilicity plays a more dominant role in the osseointegration of micro-structured titanium implants having the same surface topography at the micrometer and submicrometer scales. To understand their comparative effect on enhancing the early osseointegration of micro-rough-surfaced implants, this study compared the bone healing-promoting effect of surface strontium (Sr) chemistry that has been shown in numerous studies to super-hydrophilicity in the early osseointegration of moderately rough-surfaced clinical oral implants (SLA® implant) in rabbit cancellous bone. Material and methods Hydrothermal treatment was performed to incorporate Sr ions into the surface of clinical SLA implants (SLA/Sr implant). The surface characteristics were evaluated by using field emission-scanning electron microscopy, X-ray photoelectron spectroscopy and optical profilometry. Twenty screw implants (10 control and 10 experimental) were placed in the femoral condyles of 10 New Zealand White rabbits. The early osseointegration of the SLA/Sr implant was compared with a chemically modified super-hydrophilic SLA implant (SLActive® implant) by histomorphometric and resonance frequency analysis after 2 weeks of implantation. Results The SLA/Sr and SLActive implants exhibited an identical surface topography and average Ra values at the micron and submicron scales. The SLA/Sr implant displayed a high amount of surface Sr content (15.6 at.%). There was no significant difference in the implant stability quotient (ISQ) values between the two groups. However, histomorphometric analysis revealed a significantly higher bone-to-implant contact percentage in the SLA/Sr implants compared with the SLActive implants in rabbit cancellous bone (P

Strontium (Sr) has been successfully used for the treatment of osteoporotic bone, increasing new bone formation while reducing bone resorption by stimulating proliferation and differentiation of osteoblastic cells and inhibiting osteoclast function. In this study, Sr-incorporated Ti oxide layer was produced on clinically relevant osteoconductive implant surface, that is, a grit-blasted microrough Ti surface, by a simple hydrothermal treatment with the expectation of utilizing the osteoblast response enhancement effect of Sr for the future applications as a more osteoconductive surface of the permanent load-bearing endosseous implants, without altering the original microrough surface features of grit-blasted Ti at the micron-scale. This surface exhibits a hierarchical structure (i.e., a nanoscale surface architecture of the Sr-incorporated Ti oxide layer (SrTiO3) imposed on micron-scale rough Ti structure) and Sr ion release into physiological solution. In vitro experiments using primary mouse bone marrow stromal cells (BMSCs) revealed that the hydrothermally produced SrTiO3 coating promotes both the early and late cell response of BMSCs grown on a microrough Ti surface, with notably enhanced attachment, spreading, focal adhesion, alkaline phosphatase activity, and expression of critical integrins and osteoblastic phenotype genes. These results indicate that a hydrothermally produced SrTiO3 coating improves the osteoconductivity of the microrough Ti surface by enhancing both the early and late cell response of BMSCs. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.

Immobilization of RGD peptides on titanium (Ti) surfaces enhances implant bone healing by promoting early osteoblastic cell attachment and subsequent differentiation by facilitating integrin binding. Our previous studies have demonstrated the efficacy of RGD peptide immobilization on Ti surfaces through the electrodeposition of poly(ethylene glycol) (PEG) (RGD/PEG/Ti), which exhibited good chemical stability and bonding. The RGD/PEG/Ti surface promoted differentiation and mineralization of pre-osteoblasts. This study investigated the in vivo bone healing capacity of the RGD/PEG/Ti surface for biomedical application as a more osteoconductive implant surface in dentistry. The RGD/PEG/Ti surface was produced on an osteoconductive implant surface, i.e. the grit blasted micro-rough surface of a commercial oral implant. The osteoconductivity of the RGD/PEG/Ti surface was compared by histomorphometric evaluation with an RGD peptide-coated surface obtained by simple adsorption in rabbit cancellous bone after 2 and 4 weeks healing. The RGD/PEG/Ti implants displayed a high degree of direct bone apposition in cancellous bone and achieved greater active bone apposition, even in areas of poor surrounding bone. Significant increases in the bone to implant contact percentage were observed for RGD/PEG/Ti implants compared with RGD-coated Ti implants obtained by simple adsorption both after 2 and 4 weeks healing (P